The goal is to confirm, characterize, and identify a 60 kilodalton oncofetal phosphoprotein released from tumor cells to circulation in vivo and to culture medium in vitro and that is transiently induced and released from normal tissues after treatment of rats with carcinogens. It appears very likely that this protein will be useful for identifying the presence of tumor cells in vivo in both animals and humans and for differentiating in the animal system carcinogenic and noncarcinogenic chemicals. A biochemical assay for the factor, which is applicable to all mammalian species, is carried out on plasma due to the loss of variable amounts of activity during serum preparation. An immunoassay (ELISA) has been developed based on antibody to the rat factor, purified 800-fold from the plasma of a tumor-bearing rat. This antibody does not cross-react with the 60 kilodalton factor in cancer patient plasma, indicating that the immunoassay is more species-specific than the biochemical assay. It has not yet been purified from human sources. The 60 kilodalton phosphoprotein appears to be present in the blood plasma of all tumor-bearing animals and of all cancer patients but is absent from the blood plasma of normal animals/subjects and those with non-neoplastic diseases. It is present in the tumor. The protein is also produced in fetal tissue and is present in amniotic fluid but does not cross the placental barrier. Most relevant to carcinogenesis, a single dose of carcinogen, but not noncarcinogenic toxins, appear to transiently de-repress the gene for this oncofetal protein or cause a population of fetal-like cells to appear in the target organ. Its concentration in blood plasma peaks around 21 days post-treatment. The subsequent decline is checked if a tumor develops, its concentration then increasing in parallel with tumor size. The factor was detected in the circulation within 21 days after treatment of rats with some 12 different carcinogens. Its concentration at 21 days post-treatment is suppressed by co-administration of an anticarcinogen. As measured by the immunoassay, the concentration of the 60 kilodalton factor drops to near zero within 24 hrs of the surgical removal of a tumor. (1)